Can fingernail quality predict bone damage in Type 2 diabetes mellitus? a pilot study.

Type 2 diabetes mellitus (T2DM) adversely affects the normal functioning, intrinsic material properties, and structural integrity of many tissues, including bone. It is well known that the clinical utility of areal bone mineral density (aBMD) is limited to assess bone strength in individuals with T2DM. Therefore, there is a need to explore new diagnostic techniques that can better assist and improve the accuracy of assessment of bone tissue quality. The present study investigated the link between bone and fingernail material/compositional properties in type 2 diabetes mellitus (T2DM). For that, femoral head and fingernail samples were obtained from twenty-five adult female patients (with/without T2DM) with fragility femoral neck fractures undergoing hemi/total hip arthroplasty. Cylindrical cores of trabecular bone were subjected to micro-CT, and lower bone volume fraction was observed in the diabetic group than the non-diabetic group due to fewer and thinner trabeculae in individuals with T2DM. The material and compositional properties of bone/fingernail were estimated using nanoindentation and Fourier Transform Infrared Spectroscopy, respectively. Both bone/fingernails in T2DM had lower reduced modulus (Er), hardness (H), lower Amide I and Amide II area ratio (protein content), higher sugar-to-matrix ratio, and relatively high carboxymethyl-lysine (CML) content compared with non-diabetic patients. Sugar-to-matrix ratio and relative CML content were strongly and positively correlated with HbA1c for both bone/fingernail. There was a positive correlation between bone and fingernail glycation content. Our findings provide evidence that the degradation pattern of bone and fingernail properties go hand-in-hand in individuals with T2DM. Hence, the fingernail compositional/material properties might serve as a non-invasive surrogate marker of bone quality in T2DM; however, further large-scale studies need to be undertaken.

Droplet-Bijel-Droplet Transition in Aqueous Two-Phase Systems Stabilized by Oppositely Charged Nanoparticles: A Simple Pathway to Fabricate Bijels.

We demonstrate a novel yet straightforward methodology of stabilizing aqueous two-phase systems (ATPS) using oppositely charged nanoparticles (OCNPs). We employ commercial-grade, Ludox, OCNPs to induce self-assembly. This self-assembly route promotes the stronger adsorption of nanoparticles at the water-water interface by triggering the formation of 2D and 3D aggregates of varying sizes and shapes. The interplay of this size and shape promotes stability due to increased Gibbs detachment energy and modulates the resulting cluster adsorption at the interface, thereby the structural state of emulsions. We demonstrate the influence of polymers' and particles' composition on the structural transformation from droplet-bijel-droplet using a phase diagram. For the first time, such a structural transition and the single pathway are reported within the domain of ATPS to produce stable bijels or colloidal capsules. It is asserted that the essential condition of three-phase contact angle (θ) = 90° to favor the formation of bijels can be established by selecting a suitable experimental condition using a phase diagram without employing any complicated surface modification procedures reported in the literature. Further, the mechanistic route favoring the formation of bijels and emulsion droplets at different experimental regimes is presented based on the empirical study using turbidity and zeta potential measurements. These studies reveal that the formation of bijels will be most favored when the parameter M (ratio of weight fraction of positively charged nanoparticles to negatively charged nanoparticles) is chosen between 0.7 and 4. It is intriguing to note the fact that, while the droplets stabilized by OCNPs have shown good resilience under high centrifugal action, the bijels produced in this way continued to remain stable for a long time, offering a facile route to prepare the bijels with a hierarchical bicontinuous network structure.

Distinct Modes of Tissue Expansion in Free Versus Earlier-Confined Boundaries for More Physiological Modeling of Wound Healing, Cancer Metastasis, and Tissue Formation.

Collective cell migration is often seen in many biological processes like embryogenesis, cancer metastasis, and wound healing. Despite extensive experimental and theoretical research, the unified mechanism responsible for collective cell migration is not well known. Most of the studies have investigated artificial model wound to study the collective cell migration in an epithelial monolayer. These artificial model wounds possess a high cell number density compared to the physiological scenarios like wound healing (cell damage due to applied cut) and cancer metastasis (smaller cell clusters). Therefore, both systems may not completely relate to each other, and further investigation is needed to understand the collective cell migration in physiological scenarios. In an effort to fill this existing knowledge gap, we investigated the freely expanding monolayer that closely represented the physiological scenarios and compared it with the artificially created model wound. In the present work, we report the effect of initial boundary conditions (free and confined) on the collective cell migration of the epithelial cell monolayer. The expansion and migration aspects of the freely expanding and earlier-confined monolayer were investigated at the tissue and cellular levels. The freely expanding monolayer showed significantly higher expansion and lower migration in comparison to the earlier-confined monolayer. The expansion and migration rate of the monolayer exhibited a strong negative correlation. The study highlights the importance of initial boundary conditions in the collective cell migration of the expanding tissue and provides useful insights that might be helpful in the future to tune the collective cell migration in wound healing, cancer metastasis, and tissue formation.

Investigation of Mechanical, Material, and Compositional Determinants of Human Trabecular Bone Quality in Type 2 Diabetes.

CONTEXT: Increased bone fragility and reduced energy absorption to fracture associated with type 2 diabetes (T2D) cannot be explained by bone mineral density alone. This study, for the first time, reports on alterations in bone tissue's material properties obtained from individuals with diabetes and known fragility fracture status. OBJECTIVE: To investigate the role of T2D in altering biomechanical, microstructural, and compositional properties of bone in individuals with fragility fracture. METHODS: Femoral head bone tissue specimens were collected from patients who underwent replacement surgery for fragility hip fracture. Trabecular bone quality parameters were compared in samples of 2 groups, nondiabetic (n = 40) and diabetic (n = 30), with a mean duration of disease 7.5 ± 2.8 years. RESULTS: No significant difference was observed in aBMD between the groups. Bone volume fraction (BV/TV) was lower in the diabetic group due to fewer and thinner trabeculae. The apparent-level toughness and postyield energy were lower in those with diabetes. Tissue-level (nanoindentation) modulus and hardness were lower in this group. Compositional differences in the diabetic group included lower mineral:matrix, wider mineral crystals, and bone collagen modifications-higher total fluorescent advanced glycation end-products (fAGEs), higher nonenzymatic cross-link ratio (NE-xLR), and altered secondary structure (amide bands). There was a strong inverse correlation between NE-xLR and postyield strain, fAGEs and postyield energy, and fAGEs and toughness. CONCLUSION: The current study is novel in examining bone tissue in T2D following first hip fragility fracture. Our findings provide evidence of hyperglycemia's detrimental effects on trabecular bone quality at multiple scales leading to lower energy absorption and toughness indicative of increased propensity to bone fragility.

Development of HFD-Fed/Low-Dose STZ-Treated Female Sprague-Dawley Rat Model to Investigate Diabetic Bone Fragility at Different Organization Levels.

Type 2 diabetes (T2D) adversely affects the normal functioning, intrinsic material properties, and structural integrity of many tissues, and bone fragility is one of them. To simulate human T2D and to investigate diabetic bone fragility, many rodent diabetic models have been developed. Still, an outbred genetically normal nonobese diabetic rat model is not available that can better simulate the disease characteristics of nonobese T2D patients, who have a high prevalence in Asia. In this study, we used a combination treatment of high-fat diet (4 weeks, 58% kcal as fat) and low-dose streptozotocin (STZ; 35 mg/kg i.p. at the end of the fourth week) to develop T2D in female Sprague-Dawley (SD) rats. After 8 weeks of the establishment of the T2D model, the femoral bones were excised after euthanizing rats (animal age approximately 21 to 22 weeks; n = 10 with T2D, n = 10 without diabetes). The bone microstructure (µCT), mechanical, and material properties (three-point bending, cyclic reference point indentation, nanoindentation), mean mineral crystallite size (XRD), bone composition (mineral-to-matrix ratio, nonenzymatic cross-link ratio [NE-xLR], Fourier transform-infrared microspectroscopy), and total fluorescent advanced glycation end products were analyzed. We found that diabetic bone had reduced whole-bone strength and compromised structural properties (µCT). The NE-xLRs were elevated in the T2D group, and strongly and negatively correlated with postyield displacement, which suggests bone fragility was caused by a lack of glycation control. Along with that, the decreased mineral-to-matrix ratio and modulus, increased indentation distance increase, and wider mineral crystallite size in the T2D group were evidence that the diabetic bone composition and material properties had changed, and bone became weaker with a tendency to easily fracture. Altogether, this model simulates the natural history and metabolic characteristics of late-stage T2D (insulin resistance and as disease progress develops, hypoinsulinemia) for nonobese young (and/or adolescent) T2D patients (Asians) and provides potential evidence of diabetic bone fragility at various organization levels. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Investigation of diabetic patient's fingernail quality to monitor type 2 diabetes induced tissue damage.

Long-term Type 2 Diabetes (T2D) affects the normal functioning of heart, kidneys, nerves, arteries, bones, and joints. The T2D gradually alters the intrinsic material properties, and structural integrity of the tissues and prolonged hyperglycemia causes chronic damages to these tissues quality. Clinically no such technique is available which can assess the altered tissues quality associated with T2D. In the present study, the microstructural characterization (surface morphology, surface roughness and density and calcium content), material characterization (modulus, hardness), and macromolecular characterization (disulfide bond content, protein content and its secondary structure) are investigated among healthy, diabetic controlled (DC) and uncontrolled diabetic (UC) group of fingernail plate. It is found that T2D has an adverse effect on the human fingernail plate quality. The parameters of nail plate quality are changing in a pattern among all the three groups. The properties mentioned above are degrading in DC group, but the degradation is even worst in the case of severity of T2D (UC group) as compared to the healthy group (Healthy

Spatial Fluctuations at Vertices of Epithelial Layers: Quantification of Regulation by Rho Pathway.

In living matter, shape fluctuations induced by acto-myosin are usually studied in vitro via reconstituted gels, whose properties are controlled by changing the concentrations of actin, myosin, and cross-linkers. Such an approach deliberately avoids consideration of the complexity of biochemical signaling inherent to living systems. Acto-myosin activity inside living cells is mainly regulated by the Rho signaling pathway, which is composed of multiple layers of coupled activators and inhibitors. Here, we investigate how such a pathway controls the dynamics of confluent epithelial tissues by tracking the displacements of the junction points between cells. Using a phenomenological model to analyze the vertex fluctuations, we rationalize the effects of different Rho signaling targets on the emergent tissue activity by quantifying the effective diffusion coefficient, and the persistence time and length of the fluctuations. Our results reveal an unanticipated correlation between layers of activation/inhibition and spatial fluctuations within tissues. Overall, this work connects regulation via biochemical signaling with mesoscopic spatial fluctuations, with potential application to the study of structural rearrangements in epithelial tissues.

Anomalous stress profile in a sheared granular column.

We present measurements of the stress as a function of vertical position in a column of granular material sheared in a cylindrical Couette device. All three components of the stress tensor on the outer cylinder were measured as a function of distance from the free surface at shear rates low enough that the material was in the dense, slow flow regime. We find that the stress profile differs fundamentally from that of fluids, from the predictions of plasticity theories, and from intuitive expectation. We argue that the anomalous stress profile is due to an anisotropic fabric caused by the combined action of gravity and shear.